Thesis (Ph. D.)--University of Queensland, 2001. / Includes bibliographical references.

Thesis (M. Phil.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 101-116).

Thesis (M.S.)--Worcester Polytechnic Institute. / Keywords: antimicrobial peptides; protegrins; synthetic genes. Includes bibliographical references (p. 56-57).

Thesis (M.F.A.)--York University, 2008. Graduate Programme in Film. / Typescript. Includes filmography. Includes bibliographical references. Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR45979

published_or_final_version / Obstetrics and Gynaecology / Master / Master of Medical Sciences

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Not available / text

Not available / text

Two influenza viruses, the virulent clone 7a (H3N2) and the attenuated A/Fiji/15899/83 (H1NI) (A/Fiji), induce different level ofapoptosis in both MDCK and HeLa cells. Apoptosis induced by these two viruses could be partially inhibited by two NA inhibitors (GGI67 and DANA), when present during virus entry, but not subsequently. GGI67, which cannot enter cells, did not affect the level of infection. These results suggest that NA plays a role in influenza virus-induced apoptosis and that it acts early in the replication cycle. However, ammonium chloride, which prevents virus entry reduced the level of apoptosis induced by both viruses. In addition, amantadine, which prevents virus uncoating, inhibited apoptosis induced by the amantadine-sensitive strain A/Udorn/307/72 (H3N2). Therefore, other viral components acting intracellularly may also be involved in influenza virus-induced apoptosis. Clone 7a, A/Fiji or A/WSN/33 (H1N1)(A/WSN) proteins were expressed in HeLa cells, fused to the Herpes simplex tegument coat protein VP22. This protein has the ability to translocate from the cell in which it is synthesised to surrounding cells. Therefore, VP22- fusion proteins are delivered to a high number of cells, regardless of the level of transfection. A/WSN PB1, PB2 and HA induced significant levels ofapoptosis as did the NA, M1, M2 and NS1 proteins from clone 7a and the M1, M2, NSI and NS2 proteins from A/Fiji. Conversely, clone 7a and A/Fiji NP and A/Fiji PB2 and NA did not induce apoptosis. Confocal microscopy revealed that apoptosis was associated with fusion protein expression and that the location of the proteins corresponded with that expected during influenza virus infection. In addition, the mechanism of clone 7a NA-induced apoptosis was investigated. GGI67 inhibited apoptosis induced by the expression of clone 7a NA. Hence, NA activity is required for the induction of apoptosis. In addition, apoptosis was completely abrogated in the presence of an anti-transforming growth factor (TGF)-B antibody suggesting the activation of TGF-B during the translocation of the fusion protein from one cell to another is involved in clone 7a NA-induced apoptosis. Furthermore, clone 7a and A/Fiji NS1 proteins induced apoptosis when expressed alone, but they inhibited double-stranded (ds) RNA-induced apoptosis. However, the level of apoptosis observed in the presence of dsRNA was not reduced to background levels suggesting a pro and anti-apoptotic action of NS1 in influenza virus-infected cells. The potential mechanisms involved in the induction of apoptosis by each protein and the relevance to infection is discussed.

published_or_final_version / abstract / toc / Zoology / Master / Master of Philosophy